What are the clinical signs and laboratory findings that indicate infection in osteomyelitis?

Signs of Infection for Osteomyelitis

Osteomyelitis is diagnosed clinically when at least two of the following local signs are present: local swelling or induration, erythema >0.5 cm around the wound, local tenderness or pain, local warmth, or purulent discharge—combined with a positive probe-to-bone test in high-risk patients, which has a positive likelihood ratio of 9.2. 1, 2

Clinical Signs of Infection

Local Signs (At Least 2 Required for Diagnosis)

• Local swelling or induration over the affected bone 1
• Erythema extending >0.5 cm from the wound margin in any direction 1
• Local tenderness or pain at the site 1
• Local warmth over the affected area 1
• Purulent discharge from the wound 1

High-Specificity Physical Findings

• "Sausage toe" appearance: An erythematous, swollen, indurated digit lacking normal contours is highly suggestive of underlying osteomyelitis, particularly in diabetic foot infections 2, 3
• Visible or palpable bone through a wound has a positive likelihood ratio of 9.2 2, 3
• Positive probe-to-bone test: Using a sterile blunt metal probe, a hard, gritty sensation upon contact with bone yields a positive likelihood ratio of 9.2 in high-risk patients with clinically infected wounds 1, 2

Wound Characteristics That Increase Likelihood

• Ulcer area >2 cm² has a positive likelihood ratio of 7.2 2
• Non-healing ulcer despite ≥6 weeks of appropriate wound care and off-loading 2, 3
• Deep ulcers extending to bone or joint, especially over bony prominences (metatarsal heads, calcaneus, malleoli) 2
• Purulent drainage from a pressure injury strongly indicates underlying bone infection 2

Laboratory Findings

Serum Inflammatory Markers

• Markedly elevated ESR (>60-70 mm/hour) is suggestive of osteomyelitis and provides a likelihood ratio of 11 when combined with clinical findings 1, 2, 3
• Elevated CRP (>3.2 mg/dL) combined with ulcer depth >3 mm helps differentiate osteomyelitis from cellulitis 2, 3

Important caveat: Normal inflammatory markers do not exclude osteomyelitis and should not alter clinical suspicion when physical findings are present 2

Systemic Signs (Indicate Severe Infection)

When ≥2 of the following are present, the infection is classified as severe: 1

• Temperature >38°C or <36°C
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min
• White blood cell count >12,000/mm³ or <4,000/mm³, or >10% immature (band) forms

Critical note: Elevated white blood cell count alone is not predictive of osteomyelitis 2

Diagnostic Algorithm

Step 1: Clinical Assessment

• Inspect all wounds for visible bone, ulcer size, location over bony prominences, and healing status 2
• Perform probe-to-bone testing on every ulcer using a sterile blunt probe 2
• Assess for "sausage toe" appearance in diabetic foot ulcers 2
• Document wound characteristics including depth, area, duration, and response to therapy 2

Step 2: Laboratory Testing

• Order ESR and CRP as first-line inflammatory markers 2, 3
• Obtain two sets of aerobic and anaerobic blood cultures before starting antibiotics 3

Step 3: Imaging

• Plain radiographs first in all suspected cases, though they remain normal for 7-10 days and require >30% bone destruction to show abnormalities 2, 3
• MRI with contrast is the gold standard if radiographs are normal but clinical suspicion remains high, with 97% sensitivity and 93% specificity 2, 3, 4
• Do not delay advanced imaging by waiting for radiographic changes to develop 2

Step 4: Definitive Diagnosis

• Bone biopsy (culture + histology) is the gold standard and should be performed before initiating antimicrobial therapy when diagnostic uncertainty exists, resistant organisms are suspected, or the patient fails empiric therapy 1, 2
• Avoid soft tissue or sinus tract cultures for selecting antibiotic therapy as they do not accurately reflect bone culture results 1, 2

Common Pitfalls to Avoid

• A negative probe-to-bone test does not rule out osteomyelitis and should not preclude further evaluation 2
• Normal radiographs do not exclude osteomyelitis, especially in early presentation (first 1-2 weeks) 2, 3
• Presence or absence of typical wound infection signs (erythema, warmth) does not alter the probability of osteomyelitis 2
• Exposed bone in stage IV pressure injuries should not be used as a sole indicator, as clinical examination alone has only 22-33% sensitivity for pelvic osteomyelitis 2
• Other inflammatory conditions must be excluded: trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis, and venous stasis 1

Special Population: Diabetic Foot Osteomyelitis

Osteomyelitis is present in 50-60% of hospitalized patients with diabetic foot infections 2. Key indicators include: 2

• Swollen foot with history of ulceration
• "Sausage toe" appearance
• Chronic non-healing ulcer despite appropriate care
• Exposed bone in the ulcer base
• Infection typically spreads contiguously to involve the forefoot